The research proposed entails a multidisciplinary effort involving 24 investigators from 8 divisions of the Washington University Medical Center. The Clinical Investigation Unit, Data Processing Unit, Pathology and Experimental Animal Core Facilities, plus individual research projects described focus on the pathogenesis, management, and favorable modification of ischemic heart disease and its sequelae. Quantification of ischemia and infarction will utilize serum enzymes and CPK isoenzymes; mathematical models based on estimation theory; external evaluation of myocardial metabolism with positron-emitting isotopes of glucose and fatty acids; myocardial imaging with conventional techniques and with transaxial tomography (being developed in the Radiation Sciences Division); and evaluation of ventricular compliance. The microcirculation will be studied to seek means to maintain or restore functional myocardium after ischemia; and maintenance of the integrity of vessels in ischemic zones to facilitate effective coronary revascularization will be explored. Effects of metabolic and physiological factors on the progression of infarction will be assessed by measurement of regional myocardial heat production and mechanics in conscious dogs. Effects of angiotensin and prostaglandins on cardiac rhythm and performance will be determined. Several techniques will be used to determine whether selected interventions favorably modify ischemic injury, cardiac electrical stability, and prognosis including: 1) a quantitative, computerized, arrhythmia analysis system; 2) dynamic and static isotope imaging techniques; and 3) on-line prediction and determination of "infarct size" based on biochemical markers in serum. These studies are designed to elucidate the pathogenesis of irreversible ischemic injury and to develop improved approaches for protection of myocardium, maintenance of cardiac electrical stability, and favorable modification of prognosis in patients with ischemic heart disease.